Scientific article

IL-17E (IL-25) Enhances Innate Immune Responses during Skin Inflammation

Published inJournal of Investigative Dermatology, vol. 139, no. 8, p. 1732-1742.e17
Publication date2019

IL-17E (IL-25) is a member of the IL-17 cytokine family involved in the promotion of type 2 immune responses. Recently, IL-17E has been reported to be up-regulated in distinct skin inflammatory diseases such as psoriasis and atopic and contact dermatitis. We assessed the role played by IL-17E in skin inflammation. Here, we show that IL-17E induces skin inflammation in vivo, characterized by the expression of innate immune response genes and the recruitment of innate immune cells, particularly neutrophils. Genetic deletion or IL-17E neutralization ameliorated skin inflammation induced by imiquimod application or tape stripping, with reductions in neutrophil and macrophage infiltration as assessed by t-distributed stochastic neighbor embedding-guided multiparameter flow cytometry analysis, in mice. In humans, IL-17E promotes the recruitment of neutrophils via activation of macrophages in a p38-dependent mechanism. In addition, IL-17E is up-regulated in neutrophil-rich inflammatory skin diseases, such as pyoderma gangrenosum and acute generalized exanthematous pustulosis. Our data show a role for IL-17E in skin inflammation that is unrelated to the development of type 2 immune reactions. We propose that IL-17E is an important common denominator of chronic skin inflammation, promoting innate immune cell recruitment and activation.

  • Acute Generalized Exanthematous Pustulosis/immunology/pathology
  • Adjuvants, Immunologic/administration & dosage
  • Animals
  • Dermatitis/immunology/pathology
  • Disease Models, Animal
  • Female
  • Humans
  • Imiquimod/administration & dosage
  • Immunity, Innate
  • Interleukin-17/immunology/metabolism
  • Interleukins/genetics/immunology/metabolism
  • Macrophages/immunology/metabolism
  • Mice
  • Mice, Knockout
  • Neutrophils/immunology/metabolism
  • Pyoderma Gangrenosum/immunology/pathology
  • Skin/cytology/immunology/pathology
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases/metabolism
Citation (ISO format)
SENRA, Luisa et al. IL-17E (IL-25) Enhances Innate Immune Responses during Skin Inflammation. In: Journal of Investigative Dermatology, 2019, vol. 139, n° 8, p. 1732–1742.e17. doi: 10.1016/j.jid.2019.01.021
Main files (1)
Article (Published version)
ISSN of the journal0022-202X

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